Throughout this application various publications are referred to by partial citations within parenthesis. Full citations for these publications may be found at the end of the specification immediately preceding the claims. The disclosures of these publications, in their entireties, are hereby incorporated by reference into this application in order to more fully describe the state of the art to which this invention pertains.
The subject invention of this application, DNA encoding a human serotonin receptor (5-HT.sub.4B) and uses thereof, refers to the "5-HT.sub.4B receptor" which has been renamed to the "5-HT.sub.7 receptor" by the "Serotonin Receptor Nomenclature Committee" of the IUPHAR. Thus, all claims herein directly or indirectly related to the 5-HT.sub.4B receptor and nucleic acid molecules encoding the 5-HT.sub.4B receptor are drawn to the 5-HT.sub.7 receptor and nucleic acid molecules encoding the 5-HT.sub.7 receptor also.
Primary amino acid sequence and signal transduction data are now published for four cloned 5-HT.sub.1 -like receptors, three cloned 5-HT.sub.2 receptors, and one 5-HT.sub.3 a receptor. Analysis of the sequence homology as well as the signal transduction pathways of these receptors leads to their grouping on the basis of these attributes: The 5-HT.sub.1 subfamily includes: 5-HT.sub.1A (Fargin, 1988; Kobilka, 1989), 5-HT.sub.1B /5-HT.sub.1D.beta. (Weinshank et al., 1991 and the rest), 5-HT.sub.1D.alpha. (Branchek et al. 1991; Hamblin and Metcalf, 1991; Weinshank et al., 1992), 5-HT.sub.1E (Levy et al., 1992; McAllister et al., 1992, Zgombick et al., 1992) and 5-HT.sub.1F (Adham et al, 1993). These subtypes share &gt;50% transmembrane amino acid identity and couple to the inhibition of adenylate cyclase. The 5-HT.sub.2 family includes the 5-HT.sub.2 receptor (Pritchett et al., 1988), 5-HT.sub.1C (Julius et al., 1989) and 5-HT.sub.2F (Rat Stomach Fundus; Foguet et al., 1992; Kursar et al., 1992). These receptors share &gt;70% amino acid identity and coupling to phosphoinositide hydrolysis. The 5-HT.sub.3 receptor has been shown to be a ligand-gated ion channel (Maricq et al., 1991). Heterogeneity of 5-HT.sub.3 receptors is controversial, although other ligand-gated ion channels display significant heterogeneity. Notably absent from this series are the 5-HT.sub.4 receptors. The second messenger coupling from tissue studies indicates activation of adenylate cyclase as a primary mode of signal transduction (Dumius et al., 1988; Bockaert et al., 1990). We report here the cloning of the first mammalian 5-HT receptor that couples to the stimulation of adenylate cyclase activity which we propose to name 5-HT.sub.4B. The pharmacological properties of this receptor indicate that it may be similar to a series of functionally defined 5-HT receptors described in the porcine vena cava (Trevethick et al., 1984), cat saphenous vein, coronary arteries [Cushing and Cohen, 1992, and several vascular dilatory effects (Mylecharane and Phillips, 1989). These receptors appear to underlie contractile and relaxant responses in isolated blood vessels indicating potential therapeutic benefit in angina, coronary artery disease, atherosclerosis, and possibly cerebral blood vessel disorders leading to stroke. The presence of this subtype in the CNS also indicates potential use in disorders of higher cognitive processes as well as control of autonomic function.